title: Abnormalities in arterial-ventricular coupling in older healthy persons are attenuated by sodium nitroprusside.
abstract: The coupling between arterial elastance (E(A); net afterload) and left ventricular elastance (E(LV); pump performance), known as E(A)/E(LV), is a key determinant of cardiovascular performance and shifts during exercise due to a greater increase in E(LV) versus E(A). This normal exercise-induced reduction in E(A)/E(LV) decreases with advancing age. We hypothesized that sodium nitroprusside (SNP) can acutely ameliorate the age-associated deficits in E(A)/E(LV). At rest and during graded exercise to exhaustion, E(A) was characterized as end-systolic pressure/stroke volume and E(LV) as end-systolic pressure/end-systolic volume. Resting E(A)/E(LV) did not differ between old (70 ± 8 yr, n = 15) and young (30 ± 5 yr, n = 17) subjects because of a tandem increase in E(A) and E(LV) in older subjects. During peak exercise, a blunted increase in E(LV) in old (7.8 ± 3.1 mmHg/ml) versus young (11.4 ± 6.5 mmHg/ml) subjects blunted the normal exercise-induced decline in E(A)/E(LV) in old (0.25 ± 0.11) versus young (0.16 ± 0.05) subjects. SNP administration to older subjects lowered resting E(A)/E(LV) by 31% via a reduction in E(A) (10%) and an increase in E(LV) (47%) and lowered peak exercise E(A)/E(LV) (36%) via an increase in E(LV) (68%) without a change in E(A). Importantly, SNP attenuated the age-associated deficits in E(A)/E(LV) and E(LV) during exercise, and at peak exercise E(A)/E(LV) in older subjects on drug administration did not differ from young subjects without drug administration. In conclusion, some age-associated deficiencies in E(A)/E(LV), E(A), and E(LV), in older subjects can be acutely abolished by SNP infusion. This is relevant to common conditions in older subjects associated with a significant impairment of exercise performance such as frailty or heart failure with preserved ejection fraction.
authors.affiliation: Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Chantler
authors.forename: Amit
authors.initials: A
authors.lastname: Nussbacher
authors.forename: Gary
authors.initials: G
authors.lastname: Gerstenblith
authors.forename: Steven P
authors.initials: SP
authors.lastname: Schulman
authors.forename: Lewis C
authors.initials: LC
authors.lastname: Becker
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Jerome L
authors.initials: JL
authors.lastname: Fleg
authors.forename: Edward G
authors.initials: EG
authors.lastname: Lakatta
authors.forename: Samer S
authors.initials: SS
authors.lastname: Najjar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D003331:Coronary Vessels / Q000502:physiology*; D004548:Elasticity / Q000502:physiology*; D004562:Electrocardiography; D056966:Excitation Contraction Coupling / Q000187:drug effects* / Q000502:physiology*; D015444:Exercise / Q000502:physiology; D005260:Female; D006321:Heart / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology*; D012146:Rest / Q000502:physiology; D013318:Stroke Volume / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000502:physiology*
chemical_list: D014665:Vasodilator Agents; D009599:Nitroprusside